Addiction to drugs is a major problem worldwide. Although a variety of strategies are in use to prevent and treat drug addiction, major economic and social costs are associated with drug addiction.
Despite decades of effort focused upon developing strategies to prevent and treat drug addiction, very little success has been achieved. In the case of nicotine addiction, active behavioral interventions such as individual or group counseling or cognitive therapy alone or in combination with drug therapies such as nicotine replacement therapy (e.g., via chewing gum, transdermal patches, nasal sprays, inhalers, or lozenges), bupropion (ZYBAN™), and varenicline (CHANTIX™), have improved the rates of achieving successful quitting, but the success rates remain only 1.5- to 2.0-fold over placebo, with long term (1 yr) smoking cessation rates of only 5 to 20%. There has been a similar lack of success in the treatment of cocaine addition, and there are no small molecule, monoclonal antibody, or enzyme therapies that have been approved for treatment of cocaine addiction.
Vaccines represent another strategy to prevent and treat drug addiction, and results with vaccines against nicotine and other small molecules such as cocaine and morphine/heroin have been described (Carrera et al., Proc. Natl. Acad. Sci USA, 98: 1988-1992 (2001); Anton and Leff, Vaccine, 24: 3232-3240 (2006); Carrera et al., Nature, 378: 727-730 (1995); Hatsukami et al., Clin. Pharmacol. Ther., 78: 456-467 (2005); Maurer et al., Eur. J. Immunol., 35: 2031-2040 (2005)). A major hurdle in the development of effective vaccines is that most addictive drugs, like most small molecules, are poor immunogens. The immunogenicity of addictive drugs can be enhanced by chemically conjugating a drug (or analog thereof) to a larger molecule, such as a protein, and vaccines employing this strategy have been tested in animals and humans (see, e.g., Bonese, et al., Nature, 252: 708-710 (1974); Killian, et al., Pharmacol. Biochem. Behav., 9: 347-352 (1978); Carrera et al., Nature, 378: 727-730 (1995); Carrera et al., Proc. Nat. Acad. Sci. USA, 98: 1988-1992 (2001); Carrera et al., Proc. Nat. Acad. Sci. USA, 97: 6202-6206 (2000); Fox et al., Nat. Med., 2: 1129-1132 (1996); Kantak et al., Psychopharmacology (Berl), 148: 251-262 (2000); and Moreno et al., Mol. Pharm., 7: 431-441 (2010)). Although these approaches have had some success, they have been limited by the degree of immunity evoked by the addictive drug analog linked to the macromolecule carrier (see, e.g., Kantak et al., supra; Keyler et al., Int. Immunopharmacol., 8: 1589-1594 (2008); and Kinsey et al., Immunol. Cell Biol., 87: 309-314 (2009)).
Antibodies directed against certain addictive drugs have also been described (see, e.g., Hardin et al., J. Pharmacol. Exp. Ther., 285: 1113-1122 (1998); Proksch et al., J. Pharmacol. Exp. Ther., 292: 831-837 (2000); and Byrnes-Blake et al., Int. Immunopharmacol., 1: 329-338 (2001)).
Thus, there is a need for alternative compositions and methods to prevent or treat drug addiction. This invention provides such compositions and methods. This and other advantages of the invention will become apparent from the detailed description provided herein.